RATIONALE: Drugs used in chemotherapy, such as capecitabine and oxaliplatin, work in
different ways to stop tumor cells from dividing so they stop growing or die. Capecitabine
may stop the growth of tumor cells by stopping blood flow to the tumor. Radiation therapy
uses high-energy x-rays to damage tumor cells. Capecitabine and oxaliplatin may make tumor
cells more sensitive to radiation therapy. Combining capecitabine and oxaliplatin with
radiation therapy may kill more tumor cells.
PURPOSE: This phase II trial is studying how well giving capecitabine and oxaliplatin
together with radiation therapy works in treating patients with stage II or stage III anal
- Determine time to treatment failure in patients with stage II-IIIB squamous cell
carcinoma of the anal canal treated with capecitabine, oxaliplatin, and radiotherapy.
- Determine the toxic effects of this regimen in these patients.
- Determine the complete response rate in patients treated with this regimen.
- Determine 2-year local regional control in patients treated with this regimen.
- Determine 2-year colostomy-free survival in patients treated with this regimen.
- Determine 2-year median overall survival in patients treated with this regimen.
- Determine 2-year progression-free survival in patients treated with this regimen.
OUTLINE: Patients receive oral capecitabine* twice daily on days 1-2, 6-10, 20-24, 27-31,
and 41-42, and undergo radiotherapy* once daily on days 1-3, 6-10, 13-17, 20-24, 27-31,
34-38, and 41-42. Patients also receive oxaliplatin IV over 2 hours on days 1, 8, 22, and
29. Treatment continues in the absence of disease progression or unacceptable toxicity.
NOTE: *Patients with T3-4 lesions also receive oral capecitabine twice daily and undergo
radiotherapy once daily on days 43 and 44.
Patients are followed at 4-6 and 12 weeks and then periodically thereafter.
PROJECTED ACCRUAL: A total of 71 patients will be accrued for this study.
1. Previously untreated patients with histologically proven squamous cell carcinoma of
the anal canal.
2. AJCC stage II-IIIB (TX 1-4, NX, MO).
3. Age >/= 16 yrs old.
4. ECOG PS 0-1 (Appendix A).
5. Adequate organ function including: Absolute neutrophil Count (ANC) >/= 1,500/uL,
Platelets >/= 100,000/uL, Total bilirubin </= 1.5 x ULN, AST (SGOT)/ALT (SGPT) </= 3
x ULN, Creatinine </= 1.5mg/dL or Creatinine Clearance (CrCL) >/= 50 cc/min.
6. Patients may have measurable or non-measurable disease. Patients with measurable
disease, as defined by the modified RECIST criteria, have at least one lesion that
can be accurately measured in at least one dimension with longest diameter to be
recorded >/= 20 mm using conventional techniques or >/= 10 mm with spiral CT scan
(with minimum lesion size no less than double the slice thickness). Lesions seen on
colonoscopy or barium studies are not considered measurable lesions.
7. A negative pregnancy test in all women of child-bearing potential, within two weeks
of initiating treatment.
8. The effects of oxaliplatin and capecitabine on the developing human fetus at the
recommended therapeutic dose are unknown. For this reason and because cytotoxic
agents are known to be teratogenic, women of child-bearing potential and men must
agree to use adequate contraception (hormonal or barrier method of birth control)
prior to study entry and for the duration of study participation. Should a woman
become pregnant or suspect she is pregnant while participating in this study, she
should inform her treating physician immediately.
9. Ability to understand and the willingness to sign the written informed
1. Prior chemotherapy with oxaliplatin, capecitabine, or 5-fluorouracil.
2. Prior radiation to the pelvis.
3. Prior surgery for anal cancer excluding prior biopsy.
4. Known history of dihydropyrimidine (DPD) deficiency.
5. Known history of hypersensitivity to platinum-containing compounds.
6. Peripheral neuropathy of >/= grade 2 by Common Terminology Criteria for Adverse
Events (CTCAE) 3.0.
7. Calculated creatinine clearance (CrCl) < 50 cc/min.
8. Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, or psychiatric illness/social situations that would limit adherence with
9. Gastrointestinal tract disease resulting in an inability to take oral medication or a
requirement for IV alimentation.
10. Because there is an unknown but potential risk for adverse events in nursing infants
secondary to treatment of the mother with oxaliplatin or capecitabine, breast feeding
should be discontinued.
11. Because of the known interaction of capecitabine and coumadin, patients taking
coumadin will be ineligible. Patients will be requested to discontinue coumadin and
utilize Lovenox if agreeable. Patients must have discontinued coumadin for 7 days
before initiating therapy.
12. No prior malignancies (excluding non-melanomatous skin neoplasms) over the past 5
13. HIV-positive patients receiving combination anti-retroviral therapy are excluded from
this study because of possible pharmacokinetic interactions with capecitabine or
oxaliplatin. This exclusion is for patient safety since patients with immune
deficiency are at increased risk of lethal infections when treated with
marrow-suppressive therapy, and because very few HIV-positive anal canal cancer
patients are seen at this institution. This hinders us from accruing enough patients
to adequately test the safety of this regimen in this population.
14. Patients with symptomatic pulmonary fibrosis.